This application is for a three year project to clarify the role of serotonin (5-hydroxytryptamine [5-HT]) in suicidal behavior in adolescents. Serotonin system dysfunction may be related to suicidal behavior, so that abnormal levels of the serotonin metabolite 5-HIAA in cerebrospinal fluid (CSF) may be useful as a trait marker identifying those suicidal adolescents at risk for future attempts and even suicide completion. Two groups of inpatient adolescents (N=60) with major depressive disorder, ages 12-18 years, will be recruited to participate in an inpatient fluoxetine treatment program using standardized rating forms to assess depression, suicidal ideation and behavior. Thirty adolescents will make up a group of index "attempters" (Group 1 because of their history of a suicide attempt during the previous 12 months; an additional 30 inpatients (Group 2) with major depressive disorder but no history of suicide attempt, and will make up the "non-attempter" group. Groups 1 and 2 will begin the study with a psychiatric inpatient hospitalization, which will last approximately 4 weeks. They will have a baseline biological test battery consisting of a lumbar puncture and fenfluramine challenge tests. Thirty normal adolescents (Group 3), ages 12-18, with no history (or in first- and second-degree relatives) of depressive disorders and suicidal behavior, will be recruited as normal controls for the fenfluramine challenge and 5-HT(2) binding studies (but no lumbar punctures). Specific Aim 1 is to test the hypothesis that the suicide attempter group (Group 1, N=30) has more "blunted" prolactin responses to fenfluramine, and more 5-HT(2) binding sites (B(MAX)) than a diagnostic control group of depressed inpatient non-attempters (Group 2, N=30) and a group of normal adolescents (Group 3, N=30); in addition, for the inpatient adolescents only, that the suicide attempter group (Group 1) has significantly lower baseline levels of CSF 5-HIAA concentration than a group of depressed non-attempters; Specific Aim 2 is to assess the relation between the study's biochemical measures of serotonergic function - CSF 5-HIAA, PRL responses to fenfluramine, and 5HT(2) binding - and measures of psychopathology, depression, suicidal behavior, impulsivity and aggression.